Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: clinical role.

BACKGROUND: Current diagnosis and staging of neuroendocrine tumors (NETs) are significantly improved by the introduction of the chromogranin A (CgA) assay in plasma or serum as a tumor marker, and by the use of somatostatin receptor scintigraphy (SRS) for tumor localization. However, the clinical role of CgA assay compared with SRS in the management of NETs has not been well elucidated. PATIENTS AND METHODS: Sixty-three consecutive patients with a histological diagnosis of NET underwent plasma CgA assay and SRS for tumor staging (23 cases), evaluation of tumor response (18 cases) and evaluation of tumor recurrence on follow-up (22 cases). Twenty-one patients had well-differentiated neuroendocrine tumors (WDNETs: 18 gastroenteropancreatic tumors and three lung NETs); 22 patients had well-differentiated neuroendocrine carcinomas (WDNECs: 17 gastroenteropancreatic carcinomas, two lung neuroendocrine carcinomas and three neuroendocrine carcinomas of unknown origin) and 20 patients had poorly differentiated neuroendocrine carcinomas (PDNECs: 14 extra-pulmonary small-cell carcinomas and six Merkel cell carcinomas). Almost all (58 of 63) NETs were non-functioning. The quantitative determination of CgA was performed in plasma using an enzyme immunoassay with a cut-off value fixed at 34 U/l. Scintigraphies with indium 111-DTPA-octreotide ((111)In-pentetreotide) included whole-body images and single photon emission computed tomography (SPECT) scans of the chest and abdomen. RESULTS: SRS results were compared with CgA findings and final clinical data. The overall sensitivity of SRS and CgA, based on the final clinical data, was 77% and 55%, respectively, whereas the specificity of both SRS and CgA was 94%. Concerning tumor type, SRS accuracy was 95% for WDNETs, 86% for WDNECs and 60% for PDNECs; CgA accuracy was 76% for WDNETs, 68% for WDNECs and 50% for PDNECs. With regard to disease extent, SRS sensitivity was 100% for limited disease and 72% for advanced disease; CgA sensitivity was 43% for limited disease and 57% for advanced disease. CONCLUSIONS: In our NET series, SRS proved to be more sensitive than CgA, with equivalent specificity. Tumor differentiation influences the sensitivity of SRS and CgA analysis. In addition, the plasma CgA level is related to tumor secretory activity. Nevertheless both SRS and CgA should be considered useful tools in the diagnostic work-up of NET patients.

Efficacy of total androgen blockade in metastatic prostatic carcinoma with transient hypogonadotropic hypogonadism: a case report.

A patient affected by metastatic prostatic carcinoma and hypogonadotropic hypogonadism (HH) was treated with flutamide 750 mg/day plus an LH-RH analog. After confirmation of basal castration during treatment, he continued with antiandrogens alone. Following the normalization of gonadic function and subjective mild bone flare-up, the patient resumed the initial treatment and obtained a partial response. When flutamide was interrupted because of liver toxicity, the patient showed progressive disease in the bone, which was unresponsive to both flutamide resumption and salvage hormone therapy (bicalutamide). The patient is currently receiving chemotherapy with VP16 and estramustine phosphate and is showing both serologic (PSA) and symptomatic response. The interest of this case lies in the incidental detection of HH during therapy and in the responsiveness to treatment.

The use of thallium-201 in the preoperative detection of breast cancer: an adjunct to mammography and ultrasonography.

Thallium-201 breast scans were performed preoperatively in 72 female patients with breast abnormalities detected by mammography and/or ultrasonography (7.5-13 MHz), in order to differentiate benign from malignant breast disease. Informed consent was obtained from each patient. Scintigraphy consisted of anterior and oblique planar images of the affected breast and axilla at 10 min and 3 h following the injection of 201Tl chloride (110 MBq). All 201Tl scans were interpreted without prior knowledge of surgery data. Pathological features of breast malignancies, such as tumour size, axillary lymph node metastases, tumour grading, lymphatic vascular channel invasion and receptor status, were analysed for their association with 201Tl uptake by tumour cells. A total of 76 breast lesions were assessed in the study. On final histological diagnosis, there were 56 malignant tumours, 14 benign nodules (9 fibroadenomas, two cases of adenosis, two cases of focal fibrosis and one case of epitheliosis) and six atypical lesions (atypical ductal or lobular hyperplasia). Thallium scintigraphy was shown to have high accuracy (92%) in detecting breast cancer, better than mammography (74%) and ultrasonography (84%). Almost all (51/56) breast cancers showed greater 201Tl activity than surrounding normal breast tissue while there was no significant increase in 201Tl activity above background in all but one (19/20) case of non-malignant disease. 201Tl activity within breast tumours, calculated as tumour/background (T/B) ratio, ranged between 1.2 and 2.5 with a mean value of 1.45. In our experience the concentration of thallium in the breast cancer seems to be primarily dependent on vascularity and tumour size rather than tumour grading, lymphatic/vascular invasion or receptor status. 201Tl scan sensitivity was 97% for malignant lesions larger than 1.5 cm (n = 35) and 80% for lesions of 1.5 cm or less (n = 21); however, five of the eight breast cancers smaller than 1.0 cm were also detectable by 201Tl scintigraphy, compared with five out of seven by mammography. Thallium scintigraphy would not be useful in evaluating the axilla for lymph node metastases (sensitivity 27%, specificity 77%).

[Isolated splenic metastasis in a case of adenocarcinoma of the uterine cervix. A clinical case]. / Metastasi splenica isolata in un caso di adenocarcinoma del collo uterino. Caso clinico.

The incidence of splenic metastasis, revealed during autopsy, from solid tumours varies from 1.6% to 30% with a mean of 7%. The clinical observation of splenic metastasis in patients with carcinoma of the exocervix is only occasionally reported. In the majority of cases metastasis appears 4 or 5 years after the onset of disease. The case reported here is the only example we have found in the literature relating to an adenocarcinoma of the uterine cervix which led to an isolated splenic metastasis. A 47-years-old patient underwent radical hysterectomy according to Meigs due to a stage 1B N0 G2 endocervical adenocarcinoma. The patient was subsequently reoperated due to pelvic recurrence and received radiotherapy. Almost five years after the first operation CT showed a suspected isolate splenic recidivation following pain in the left side. Hepatosplenic scintigraphy confirmed the presence of a large central cold area, with blurred edges, suggesting metastasis. The patient again underwent laparotomy: the volume of the spleen was found to be increased with the splenic hilum covered with neoplastic tissue. Splenectomy was performed. Abdomino-pelvic and retroperitoneal inspection showed no further signs of metastasis. Histological tests confirmed the massive metastasis of the adenocarcinoma in splenic parenchymal tissue which was relatively differentiated with a clear cell appearance. Seven months later the patient was again operated following intestinal occlusion due to numerous entero-enteric adhesions. During the course of surgery a micronodule was removed from the cholecystic serosa, apparently composed of fibrin; histological analysis proved that this micronodule was the site of glandular micrometastasis. The patient then began three cycles of chemotherapy with Adriamycin (60 mg/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of immunoscintigraphy in the follow-up of surgically treated gastrointestinal carcinomas using 111In-labelled anti-CEA monoclonal antibodies.

Twenty-five patients treated surgically for gastrointestinal carcinomas (16 rectum-sigmoid colon, 6 colon, 3 stomach) were investigated by immunoscintigraphy (IS) using 111In-labelled anti-CEA antibody (mouse monoclonal F023C5) F(ab')2 fragments in order to visualize questionable abdominopelvic recurrences (excluding the liver). Fifteen (60%) patients showed a rise in serum CEA levels above 5 ng/ml. Planar scans and emission computed tomographic (ECT) imaging were carried out without reference to the results of computed tomographic (CT) scans and gastrointestinal endoscopic examinations done 1-2 weeks before IS. Final diagnoses were based on biopsies and autopsies (13 cases) or on follow-up findings over at least 2 years (12 cases). Sixteen patients had a final diagnosis of recurrent malignant disease in the extrahepatic abdomen or pelvis. Of these, six were correctly diagnosed by both IS and conventional diagnostic procedures, six by IS only and two by conventional methods only. Two tumour recurrences remained undetected by both diagnostic approaches. However, five tumour recurrences were detected by IS more than 4 months earlier than by any other diagnostic procedures performed during clinical follow-up. Of the nine disease-free patients (disregarding the liver) three were correctly identified by both IS and the other diagnostic methods, four by IS only and two by conventional diagnostic procedures only. Overall sensitivity (75%) and specificity (89%) of 111In-IS were higher than figures obtained using CT scanning and endoscopy (50% and 78% respectively). True positive IS was observed in 6/15 (40%) CEA seropositive patients and in 6/10 (60%) CEA seronegative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnostic value of echography in the study of thyroid nodules. Ultrasonographic and histological findings on 103 "cold" nodules]. / Valore diagnostico della ecografia nello studio dei nodi tiroidei.

This study examines the accuracy of ultrasonic scanning in the recognition of malignancy in 103 "cold" thyroid nodules. All nodules underwent to surgical ablation and to histopathological examination. 10 nodules were cistic, 72 solid and 21 mixed cistic-solid on echography. None of the cistic nodules showed malignant disease while six carcinomas were present in solid nodules and one (a papillary cancer) in a mixed cistic-solid lesion. However we were unable to find echographic abnormalities pathognomonic for malignancy. Only in one case (an undifferentiated carcinoma which involved adjacent blood vessels) the diagnosis of malignant tumour was made before operation; in the other cases the echo patterns of the carcinomatous nodules were similar to those observed in benign nodules. Similar ultrasonic findings were also seen in the various types of thyroid cancer (3 follicular, 2 papillary, 1 medullary, 1 undifferentiated) a part the papillary carcinoma which appeared as cistic-solid lesion. Our data seem to limit the diagnostic value of echography in the detection of malignant thyroid nodules, nevertheless they confirm the benignancy of echografically cistic nodules.

Twenty-four hour variations of triiodothyronine (T3) levels in patients who had thyroid ablation for thyroid cancer, receiving T3 as suppressive treatment.

Measurements of serum triiodothyronine (T3) concentrations were made in 46 patients who had thyroid ablation for thyroid cancer and who were receiving T3 three times a day as suppressive treatment. In all patients thyrotropin (TSH) suppression was confirmed by the inhibition of TSH response to thyrotropin releasing hormone (TRH). The suppressive dose of T3 varied from 40 to 100 micrograms/day (mean +/- SD 72.39 +/- 13.07 micrograms/day). Related to body weight the dose varied from 0.95 to 1.35 micrograms/kg/day (mean +/- SD 1.13 +/- 0.13 micrograms/kg/day). In ten hospitalized patients serum T3 levels were measured at hourly intervals from 08:00 to 23:00. Before the first dose of T3, serum T3 levels were 153 +/- 43 mg/100 ml; after T3 the levels increased promptly reaching after 4 h a peak of 264 +/- 90 ng/100 ml. Afterwards T3 levels showed a similar peak after each dose: 262 +/- 77 and 266 +/- 78 ng/100 ml, slightly decreasing in the intervals between the doses: 227 +/- 63 and 255 +/- 69 ng/100 ml. After the last peak T3 levels showed a slow decline during the night. TSH response to TRH was completely inhibited both at 08:00 and at 16:00. In 36 outpatients T3 levels were measured twice a day and T3 levels were found similar to the ones of the first group. In these patients also TSH response to TRH evaluated at 08:00 was completely inhibited. No important side effect was noted in both groups of patients.

[Clinical comparison of the kinetics of 99mTc pyrophosphate and 99mTc methylene diphosphonate (author's transl)]. / Confronto clinico delle cinetiche di 99mTc-pirofosfato e 99mTc-metilendifosfonato.

In a series of 10 patients the hematic and plasmatic clearances of 99mTc-pyrophosphate (PYP) and 99mTc-metylene-diphosphonate (MDP) have been studied. The analysis of the results shows that the elimination both hematic and plasmatic of MDP is significantly faster than that of PYP. Moreover the plasmatic elimination of PYP is faster than its hematic elimination. This fact is probably due to a partial absorption of the radionuclide on the surface of the red cells. No significant differences result in the urinary elimination of both radionuclides. As a consequence the MDP has a lower fundus activity and a lower irradiation dose to the blood and to the whole body. For those reasons this radionuclide is proposed as the preferred agent in bones scintigraphy.